Amyloid-β Peptides are Generated in Mitochondria-Associated Endoplasmic Reticulum Membranes

Article type: Short Communication

Authors: Schreiner, Bernadette^{; 1} | Hedskog, Louise^{; 1} | Wiehager, Birgitta | Ankarcrona, Maria^{; *}

Affiliations: Karolinska Institutet, Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division for Neurogeriatrics, Stockholm, Sweden

Correspondence: [*] Correspondence to: Dr. Maria Ankarcrona, Karolinska Institutet, Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division for Neurogeriatrics, Novum, Blickagången 6, SE-14157 Huddinge, Sweden. Tel.: +46 8 585 83617; Fax: +46 8 585 83610; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Extracellular aggregates of amyloid-β peptides (Aβ) are a hallmark in Alzheimer's disease (AD) brains. Recent findings suggest that Aβ is generated intracellularly and potential production sites include endosomes and trans-Golgi network. We determined the production of Aβ in subcellular fractions isolated from mouse brain. We found that a considerable amount of Aβ is produced at mitochondria-endoplasmic reticulum (ER) contact sites including outer mitochondrial membrane and mitochondria-associated ER membranes. Enhanced Aβ production at this site may disturb ER, mitochondrial and mitochondria-ER contact site function. This may be one key step in the cascade of events eventually leading to neurodegeneration in AD.

Keywords: Alzheimer's disease, endoplasmic reticulum (ER), intracellular amyloid-β peptides, mitochondria-ER contact sites, mitochondria, mitochondria-associated ER membranes (MAM)

DOI: 10.3233/JAD-132543

Journal: Journal of Alzheimer's Disease, vol. 43, no. 2, pp. 369-374, 2015